The Synaptic Modulation of Anxiety Experiences


What we know as anxiety is often misinterpreted as referring to the diagnosis of an anxiety disorder. Whilst some might use the word to refer to an abnormal state of anxiety, generally the word anxiety refers to the body’s natural response to stress. As humans, we are prone to feel anxious in ‘threatening’ situations – this is a survival instinct, and a healthy one at that – but what really determines our experience of anxiety-like behaviour?

A synapse, also known as a neural junction, is the site of electric nerve impulse transmission between two nerve cells (neurons) or between a neuron and a gland or muscle cell. Due to the large number of genes, proteins and neural types involved, the mechanisms behind the organisation of neural synapses remain unclear.

In a recent study, scientists at Daegu Gyeongbuk Institute of Science and Technology used genetically modified mice to investigate the role of two proteins in regulating the development of inhibitory synapses in the hippocampus in the context of anxiety-related behaviours, paving the way for a more complete understanding of the brain.

The proper functioning of our brain, as well as the brains of other animals, is dependent on a complex interplay of multiple types of neurons. These interactions are organised by many synaptic proteins; it is therefore extremely challenging to determine their specific functions.

The ability of synapses to strengthen or weaken depending on the amount of activity present is called synaptic plasticity. Synapse plasticity is crucial to the proper response of animals and their behavioural adaptation to their environments. Several studies over the past decade have examined two proteins that are related to GABA-mediated synapses in mammals.

The first of the two, Npas4, is involved in shaping inhibitory synapse organisation, but it also has a variety of other functions in the brain.

IQSEC3, on the other hand, is only found in ‘GABAergic’ (GABA modifying) synapses and is thought to be a target of Npas4, though this has not been proven conclusively in live animals.

In a recent study published in Cell Reports, a group of scientists from Daegu Gyeongbuk Institute of Science and Technology (DGIST) in Korea report findings from a mouse study that shed light on the specific functions of Npas4 and IQSEC3 in the hippocampus.

The researchers showed that Npas4 increases the expression of IQSEC3 and facilitates the organisation of GABAergic synapses in specific hippocampal neurons in neuronal cell cultures and mice.

Secondly, scientists observed that specific GABAergic synapses organised by Npas4 and IQSEC3 were directly linked to anxiety-like behaviours, through behavioural trials, and subsequent chemogenetic approaches applied to genetically modified mice.

Control mice responded differently in an anxiety-inducing environment, but mice with dysregulated IQSEC3 expression did not.

These findings are said to shed light on how abnormalities in anxious behaviours can be found to further develop circuit based therapeutic approaches to correct them.

The researchers intend to use even more sophisticated genetic approaches to continue investigating the role of IQSEC3 in various types of synapses and neural circuits.

The more we learn about the role of specific synaptic proteins, the closer we get to forming a wider understanding of the neural networks behind our behaviour.

Want to find out more about the science behind anxiety? Check out this video:

Original Source:  Kim, S., Park, D., Kim, J., Kim, D., Kim, H., Mori, T., Jung, H., Lee, D., Hong, S., Jeon, J., Tabuchi, K., Cheong, E., Kim, J., Um, J.W. and Ko, J. (2021). Npas4 regulates IQSEC3 expression in hippocampal somatostatin interneurons to mediate anxiety-like behavior. Cell Reports, 36(3), p.109417.

F‌eatured Image: Photo by Pixabay from Pexels

Edited by Cyrus Rohani-Shukla

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